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Advances in Nutrition and Cancer pp 401–426Cite as

Inflammatory Angiogenesis and the Tumor Microenvironment as Targets for Cancer Therapy and Prevention

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Part of the book series: Cancer Treatment and Research ((CTAR,volume 159))

Abstract

In addition to aberrant transformed cells, tumors are tissues that contain host components, including stromal cells, vascular cells (ECs) and their precursors, and immune cells. All these constituents interact with each other at the cellular and molecular levels, resulting in the production of an intricate and heterogeneous complex of cells and matrix defined as the tumor microenvironment. Several pathways involved in these interactions have been investigated both in pathological and physiological scenarios, and diverse molecules are currently targets of chemotherapeutic and preventive drugs. Many phytochemicals and their derivatives show the ability to inhibit tumor progression, angiogenesis, and metastasis, exerting effects on the tumor microenvironment. In this review, we will outline the principal players and mechanisms involved in the tumor microenvironment network and we will discuss some interesting compounds aimed at interrupting these interactions and blocking tumor insurgence and progression. The considerations provided will be crucial for the design of new preventive approaches to the reduction in cancer risk that need to be applied to large populations composed of apparently healthy individuals.

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Abbreviations

IGF1-R:

Insulin-like growth factor 1-receptor

IκB:

Inhibitor kinase B

IKK:

Inhibitor kinase kinase

IL-13:

Interleukin-13

IL-4:

Interleukin-4

IL-6:

Interleukin-6

IL-12:

Interleukin-12

IL1Rα:

Interleukin-1 receptor-alpha

IL1β:

Interleukin-1 beta

JAK:

Activating Janus kinase

MAPK:

Mitogen-activated phospho kinase

MDM2:

Murine double minute 2

MDM4:

Mouse double minute 4

MDSC:

myeloid-derived suppressor cell

MMP-1:

Matrix metallo protease-1

MMP-2:

Matrix metallo protease-2

MMP-7:

Matrix metallo protease-7

MMP-9:

Matrix metallo protease-9

mTOR:

Mammalian target of rapamycin

N1:

N1-polarized neutrophils

N2:

N2-polarized neutrophils

NAC:

N-acetylcysteine

NF-κB:

Nuclear factor-kappa B

NSAIDs:

Non-steroidal anti-inflammatory drugs

NSCLC:

Non-small cell lung cancer

PDGF:

Platelet-derived growth factor

PDGFR-β:

Platelet-derived growth factor receptor-beta

PDGFR:

Platelet-derived growth factor receptor

PI3K:

Phosphoinositide 3-kinase

PIG3:

p53-inducible gene 3

PlGF:

Placental growth factor

PMNs:

Polymorphonuclear neutrophils

Raf:

Root abundant factor

RARs:

Retinoid acid receptors

RARβ:

Retinoid acid receptor-beta

RCC:

Renal cell carcinoma

RelA:

NFkB subunit-A

RelB:

v-rel reticuloendotheliosis viral oncogene homolog B

RET:

Rearranged during transfection

RHD:

Rel homology domain

RITA:

Reactivation of p53 and induction of tumor cell apoptosis

ROS:

Reactive oxygen species

RTK:

Receptor tyrosine kinase

STAT:

Signal transducer and activator of transcription

STAT3:

Signal transducer and activator of transcription 3

SV40:

Simian virus 40

TAM:

Tumor-associated macrophage

TEM:

Tie2-expressing macrophage

TGFα:

Transforming growth factor-alpha

TGFβ:

Transforming growth factor-beta

Th:

T helper

Th2:

T helper type-2 polarization

TKIs:

Tyrosine kinase inhibitors

TNF:

Tumor necrosis factor

TNFα:

Tumor necrosis factor-alpha

TP53TG1:

TP53 target 1

TSP-1:

Thrombospondin-1

VEGF-A:

Vascular endothelial growth factor A isoform

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

vSMC:

Vascular smooth muscle cell

WIP1:

Wound-induced protein 1

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Acknowledgments

These studies were supported by grants from the AIRC (Associazione Italiana per la Ricerca sul Cancro), the Ministero della Salute, the and ISS (Istituto Superiore della Sanità). AB is a FIRC (Fondazione Italiana per la Ricerca sul Cancro) fellow. AP is the recipient of the “Caterina Forni” AIRC fellowship. We thank Dr Paola Corradino (Multimedica IRCCS) for data management.

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Authors and Affiliations

  1. Polo Scientifico e Tecnologico, MultiMedica Onlus, Milano, Italy

    Antonino Bruno & Arianna Pagani

  2. Research Infrastructure, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy

    Teresa Rossi & Adriana Albini

  3. Department of Biotechnologies and Life Sciences, University of Insubria, Varese, Italy

    Arianna Pagani & Douglas M. Noonan

  4. Polo Scientifico e Tecnologico, MultiMedica IRCCS, Milano, Italy

    Elena Magnani, Douglas M. Noonan & Anna Rita Cantelmo

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  1. Antonino Bruno
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  3. Elena Magnani
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  4. Teresa Rossi
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  5. Douglas M. Noonan
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  7. Adriana Albini
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Correspondence to Adriana Albini .

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Editors and Affiliations

  1. Dept. of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

    Vincenzo Zappia

  2. Clinical and Experimental Medicine, University of Naples "Federico II", Naples, Italy

    Salvatore Panico

  3. Institute of Food Sciences National Research Council, Avellino, Italy

    Gian Luigi Russo

  4. Dept. of Experimental Oncology, National Cancer Institute, Naples, Italy

    Alfredo Budillon

  5. Dept. of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

    Fulvio Della Ragione

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Bruno, A. et al. (2014). Inflammatory Angiogenesis and the Tumor Microenvironment as Targets for Cancer Therapy and Prevention. In: Zappia, V., Panico, S., Russo, G., Budillon, A., Della Ragione, F. (eds) Advances in Nutrition and Cancer. Cancer Treatment and Research, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38007-5_23

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